You woke up, felt fresh air on your face as you walked out the door,

花一點時間想想你的一天

encountered new colleagues and had great discussions,

早上你醒來,走出家門口,感覺清新空氣輕拂過你的臉龐.

and felt in awe when you found something new.

巧遇你的一些新同事並和他們相談甚歡、

But I bet there's something you didn't think about today --

也為新奇的事物目瞪口呆.

something so close to home

但我敢打賭,有一些東西你今天絕對沒想到-

that you probably don't think about it very often at all.

有些東西是如此貼近您,

And that's that all the sensations, feelings,

以至於很多時候你根本忽略它的存在.

decisions and actions

那就是你所有的一切喜怒哀樂,一切感覺,

are mediated by the computer in your head

所有的決定和行動

called the brain.

都是被你腦袋裡的電腦所控制.

Now the brain may not look like much from the outside --

也就是你的大腦.

a couple pounds of pinkish-gray flesh,

大腦看起來和它的外表大不同--

amorphous --

是幾英磅粉紅偏灰色的肉，

but the last hundred years of neuroscience

無特定形狀--

have allowed us to zoom in on the brain,

但近百年來神經科學的研究

and to see the intricacy of what lies within.

使我們能夠放大細究大腦，

And they've told us that this brain

看到大腦內的複雜構造.

is an incredibly complicated circuit

過往的研究告訴我們,

made out of hundreds of billions of cells called neurons.

大腦是由數千億的神經元細胞

Now unlike a human-designed computer,

組造成一個令人難以置信的複雜電路.

where there's a fairly small number of different parts --

不同於人為設計的電腦,

we know how they work, because we humans designed them --

只由相當少數的零件組成、

the brain is made out of thousands of different kinds of cells,

知道它們是如何運作,因為那是我們人類所設計的

maybe tens of thousands.

而大腦是由數千種不同種類的細胞架構的，

They come in different shapes; they're made out of different molecules.

或許有數萬種吧。

And they project and connect to different brain regions,

它們各有不同的形狀,是由不同的分子組成，

and they also change different ways in different disease states.

各自連結到大腦不同的區域。

Let's make it concrete.

會隨著不同疾病狀態而呈現不同的改變.

There's a class of cells,

讓我更進一步解釋.

a fairly small cell, an inhibitory cell, that quiets its neighbors.

有一類細胞,是一種相當小的、

It's one of the cells that seems to be atrophied in disorders like schizophrenia.

具抑制作用的細胞,專門控制它的鄰居,使大家安靜下來守紀律.

It's called the basket cell.

在精神分裂症患者腦部被發現萎縮的細胞種類之一.

And this cell is one of the thousands of kinds of cell

也就是所謂的籃狀細胞。

that we are learning about.

是我們正在學習瞭解中的

New ones are being discovered everyday.

數千種細胞其中之一.

As just a second example:

還有更多新種類的細胞每天不斷地被發掘。

these pyramidal cells, large cells,

這是第二個例子：

they can span a significant fraction of the brain.

這些是錐體細胞,很大的細胞，

They're excitatory.

它們覆蓋大腦很大一部分.

And these are some of the cells

它們具有興奮性.

that might be overactive in disorders such as epilepsy.

當癲癇患者發病時,

Every one of these cells

這類細胞都可能有些過度活躍.

is an incredible electrical device.

每一個腦神經細胞都像是

They receive input from thousands of upstream partners

一種巧奪天工的電子器材。

and compute their own electrical outputs,

它們接收上千個上游腦神經細胞傳來的訊息

which then, if they pass a certain threshold,

規劃整理出自己的電子訊號,

will go to thousands of downstream partners.

然後等到訊號強過臨界點後,

And this process, which takes just a millisecond or so,

就會把訊號傳送給成千上萬的下游細胞.

happens thousands of times a minute

而這個過程,只需要一毫秒左右，

in every one of your 100 billion cells,

而且每分鐘發生幾千次,

as long as you live

同部在腦中1千億個腦細胞之間進行.

and think and feel.

只要你還活著,

So how are we going to figure out what this circuit does?

有思想、有感覺都是如此.

Ideally, we could go through the circuit

那麼我們如何能確認這個電路各扮演什麼角色呢?

and turn these different kinds of cell on and off

理想的情況下,我們可以通過電路,

and see whether we could figure out

開啟或關閉這些不同類型的細胞

which ones contribute to certain functions

看看我們能否找出

and which ones go wrong in certain pathologies.

它們各自特殊的功能,

If we could activate cells, we could see what powers they can unleash,

或是當它們表現不正常時,所產生的那些病癥.

what they can initiate and sustain.

如果我們可以啟動某些細胞,我們就知道它們可以發揮什麼能力、

If we could turn them off,

什麼功能是它們可以啟動或維持的.

then we could try and figure out what they're necessary for.

如果我們可以將它們關閉，

And that's a story I'm going to tell you about today.

我們就可以試著弄清楚他們對我們的必要性是什麼。

And honestly, where we've gone through over the last 11 years,

這就是今天我要告訴你的故事.

through an attempt to find ways

真的,超過11年的研究經歷中,

of turning circuits and cells and parts and pathways of the brain

我們企圖尋找方法

on and off,

去開關腦中的電路、細胞、任何小部份

both to understand the science

和它們傳導的途徑.

and also to confront some of the issues

不僅是為了滿足對科學的好奇心

that face us all as humans.

也為了正視、解決人類現在

Now before I tell you about the technology,

所面臨的一些問題.

the bad news is that a significant fraction of us in this room,

現在，在我開始告訴你有關的科技之前,

if we live long enough,

我要告訴您一個壞消息,在這房間裡的不少人

will encounter, perhaps, a brain disorder.

如果活的夠久

Already, a billion people

他們的大腦就會有機會紊亂,不聽指揮.

have had some kind of brain disorder

目前,約有十億人

that incapacitates them,

已經得了大腦病變，

and the numbers don't do it justice though.

以至他們癱瘓殘障。

These disorders -- schizophrenia, Alzheimer's,

而數字無法真切代表出疾病的嚴重性.

depression, addiction --

這些疾病-精神分裂症，阿茲海默老年癡呆症、

they not only steal our time to live, they change who we are.

憂鬱症，癮癖-

They take our identity and change our emotions

疾病不僅偷走我們的生命,還改變我們的人格

and change who we are as people.

不僅剽竊走我們的自我認知，還改變我們的情緒--

Now in the 20th century,

讓我們變成另一個人。

there was some hope that was generated

20世紀的今天,

through the development of pharmaceuticals for treating brain disorders,

由於治療腦部疾病的新藥品

and while many drugs have been developed

不斷被研發出來,為我們帶來一絲希望。

that can alleviate symptoms of brain disorders,

縱使已有許多藥物能

practically none of them can be considered to be cured.

緩解腦部疾病的的症狀，

And part of that's because we're bathing the brain in the chemical.

幾乎沒有任何一種能被認為可以完全治癒腦部病變。

This elaborate circuit

部分的原因是因為，服藥就好似把大腦浸泡在化學藥劑中

made out of thousands of different kinds of cell

但是腦部內精心設計的電路是由

is being bathed in a substance.

數千種不同的細胞組成

That's also why, perhaps, most of the drugs, and not all, on the market

卻都被浸泡在同一種液體中.

can present some kind of serious side effect too.

這也是為什麼,市場上的許多藥物，並不是所有的，

Now some people have gotten some solace

都會引起一些嚴重的副作用

from electrical stimulators that are implanted in the brain.

現在有些人把電極植入大腦中

And for Parkinson's disease,

刺激腦細胞來改善某些疾病的症狀.

Cochlear implants,

的確對於像帕金森氏症病患，

these have indeed been able

由耳蝸植入電極

to bring some kind of remedy

確實能夠帶來

to people with certain kinds of disorder.

某種程度的緩解,

But electricity also will go in all directions --

降低病人的身體殘礙的程度.

the path of least resistance,

但是電流波會導向各個方向-

which is where that phrase, in part, comes from.

而且"專撿軟柿子捏"，傳向阻礙力最小的通路

And it also will affect normal circuits as well as the abnormal ones that you want to fix.

想來這也可能是這句名言的起源.

So again, we're sent back to the idea

電流也有可能影響到正常的電路,不只在我們想修復的不正常處.

of ultra-precise control.

所以問題回到

Could we dial-in information precisely where we want it to go?

極精密的控制上.

So when I started in neuroscience 11 years ago,

我們可不可能只把訊息傳送到標靶區呢?

I had trained as an electrical engineer and a physicist,

11年前,當我開始投入神經科學研究時，

and the first thing I thought about was,

我已受過電氣工程師和物理學家的訓練，

if these neurons are electrical devices,

所以首先我想到是，

all we need to do is to find some way

如果這些神經元都是電氣設備的話，

of driving those electrical changes at a distance.

我們須要做的只是找到某種方式,

If we could turn on the electricity in one cell,

在一定距離中傳送電流的變化到目的地.

but not its neighbors,

如果我們能使某一個細胞的電路被打開,

that would give us the tool we need to activate and shut down these different cells,

而不要干擾到它的鄰居們.

figure out what they do and how they contribute

這將讓我們有能力去活化或催眠不同的各種細胞,

to the networks in which they're embedded.

進而瞭解它們的功能和對

And also it would allow us to have the ultra-precise control we need

整體腦神經系統的貢獻.

in order to fix the circuit computations

同時也允許我們去執行極精密的控制,

that have gone awry.

以修改腦中出了錯的

Now how are we going to do that?

電路運算.

Well there are many molecules that exist in nature,

那我們該怎麼做呢？

which are able to convert light into electricity.

自然界中存有很多小分子，

You can think of them as little proteins

能夠將光能轉化成電能.

that are like solar cells.

你可以把它們想像成類太陽能電池

If we can install these molecules in neurons somehow,

的微小蛋白質。

then these neurons would become electrically drivable with light.

如果我們將這些分子安裝在神經元內

And their neighbors, which don't have the molecule, would not.

那麼這些神經元將可以被光驅動

There's one other magic trick you need to make this all happen,

而相鄰的神經細胞因為不具有這些轉化分子不會被活化.

and that's the ability to get light into the brain.

但是還需要一個神奇的技術配合一切才能成功.

And to do that -- the brain doesn't feel pain -- you can put --

那就是怎麼讓光進入腦中啊!

taking advantage of all the effort

並且要做到這-把光導入大腦而不引起疼痛--

that's gone into the Internet and communications and so on --

我們運用腦中本有的

optical fibers connected to lasers

互聯網和其溝通能力等等功能-

that you can use to activate, in animal models for example,

將光纖連接到雷射光

in pre-clinical studies,

使我們能夠精準的利用光束來啟動細胞

these neurons and to see what they do.

讓我們從臨床實驗前期的動物研究中

So how do we do this?

知道各神經元扮演的角色.

Around 2004,

那麼,如何才能做到這一點？

in collaboration with Gerhard Nagel and Karl Deisseroth,

大約在2004年,

this vision came to fruition.

在與吉爾 納格(Gerhard Nagel),和卡爾 得許窪多(Karl Deisseroth) 的合作中

There's a certain alga that swims in the wild,

一切的構想終於開花結果

and it needs to navigate towards light

我們發現一種野生的藻類

in order to photosynthesize optimally.

它們會自動導航向光源游去,

And it senses light with a little eye-spot,

好讓自身的光合作用發揮到最佳狀態。

which works not unlike how our eye works.

它感光系統是一個光感眼點,

In its membrane, or its boundary,

跟我們的眼睛運作方法不同.

it contains little proteins

在眼點的外膜,或者其周圍，

that indeed can convert light into electricity.

含有這些小蛋白質

So these molecules are called channelrhodopsins.

可以將光能轉化成電能。

And each of these proteins acts just like that solar cell that I told you about.

這些分子被稱為:視紫質管道(channelrhodospins).

When blue light hits it, it opens up a little hole

這些蛋白質就像我之前說的跟太陽能電池的功能一樣。

and allows charged particles to enter the eye-spot,

當藍光照射到它,它會開一個小洞，

and that allows this eye-spot to have an electrical signal

讓帶電粒子進入眼點。

just like a solar cell charging up a battery.

然後眼點就能產生電子信號，

So what we need to do is to take these molecules

就像太陽能電池充電的道理一樣。

and somehow install them in neurons.

因此,我們需要做的就是把這些分子，

And because it's a protein,

想辦法安裝在神經元中。

it's encoded for in the DNA of this organism.

而且因為它是一種蛋白質，

So all we've got to do is take that DNA,

而有關的DNA可以從藻類中被拆解出

put it into a gene therapy vector, like a virus,

所以我們要做的就是採取這段DNA，

and put it into neurons.

利用基因治療的運輸工具,像是病毒,

So it turned out that this was a very productive time in gene therapy,

攜帶進腦神經元中.

and lots of viruses were coming along.

剛巧那幾年基因治療正蓬葧發展，

So this turned out to be very simple to do.

多種不同的病毒都可被利用.

And early in the morning one day in the summer of 2004,

我們發現原來這非常簡單容易

we gave it a try, and it worked on the first try.

在2004年夏天的一個早上,

You take this DNA and you put it into a neuron.

是我們第一次嘗試這個實驗,而且一舉成功。

The neuron uses its natural protein-making machinery

我們把DNA送進神經元中,

to fabricate these little light-sensitive proteins

神經元則利用它自己本有的蛋白質製造裝置

and install them all over the cell,

編造出許多小感光蛋白質,

like putting solar panels on a roof,

很快的整個神經元細胞都佈滿了這種蛋白質,

and the next thing you know,

就像在屋頂上安裝太陽能電池板一樣。

you have a neuron which can be activated with light.

不用多久,

So this is very powerful.

我們就有個能被光活化的神經元.

One of the tricks you have to do

這是非常有價值的發現.

is to figure out how to deliver these genes to the cells that you want

其中一個關鍵的技巧是必須要準確地

and not all the other neighbors.

將感光DNA傳送到某些特定腦神經元中的，

And you can do that; you can tweak the viruses

而不是它們的左鄰右舍們。

so they hit just some cells and not others.

而我們可以這樣做:我們可以調整變換病毒

And there's other genetic tricks you can play

讓病毒只去襲擊某些特定的神經元。

in order to get light-activated cells.

當然也可以利用其他生物基因工程的技術

This field has now come to be known as optogenetics.

來獲得可被光活化細胞。

And just as one example of the kind of thing you can do,

這個領域現在被稱為光電遺傳學(optogenetics)。

you can take a complex network,

舉個例子來說,你可以這樣做,

use one of these viruses to deliver the gene

你可以在一個複雜的網絡系統中，

just to one kind of cell in this dense network.

使用一種病毒去輸送基因到特定的一類細胞內

And then when you shine light on the entire network,

即使是在高密度的細胞社區裡也能達成.

just that cell type will be activated.

然後用光去照射整個細胞社區,

So for example, lets sort of consider that basket cell I told you about earlier --

而只有那種具感光蛋白質的細胞會被活化.

the one that's atrophied in schizophrenia

好!讓我們用之前所提過的籃狀細胞為例子--

and the one that is inhibitory.

就是那種具有抑制作用、精神分裂症者身上

If we can deliver that gene to these cells --

萎縮的細胞。

and they're not going to be altered by the expression of the gene, of course --

如果我們能夠將感光基因送到籃狀細胞內--

and then flash blue light over the entire brain network,

當然前提是它們不會因感光基因而突變--

just these cells are going to be driven.

-然後當我們用藍光照射所有腦細胞時,

And when the light turns off, these cells go back to normal,

只有籃狀細胞會被驅動活化.

so they don't seem to be averse against that.

把光線關閉後,籃狀細胞則會恢復正常，

Not only can you use this to study what these cells do,

不會產生不良的副作用。

what their power is in computing in the brain,

我們不僅可利用這技術去研究這些細胞在做什麼，

but you can also use this to try to figure out --

它們在大腦內如何跟別種細胞協調互動，

well maybe we could jazz up the activity of these cells,

而且也可以試著利用這技術去找到如何:

if indeed they're atrophied.

讓已經萎縮的細胞興奮起來、

Now I want to tell you a couple of short stories

手舞足蹈。

about how we're using this,

現在我想告訴你一兩個有關於我們如何利用

both at the scientific, clinical and pre-clinical levels.

這項技術的故事,

One of the questions we've confronted

都是應用在科學,臨床和臨床前的試驗.

is, what are the signals in the brain that mediate the sensation of reward?

我們所面臨的其中一個問題是:

Because if you could find those,

在腦中的什麼信號會挑起被嘉獎的感覺?

those would be some of the signals that could drive learning.

因為如果我們知道就可以利用

The brain will do more of whatever got that reward.

這種信號去驅動細胞學習.

And also these are signals that go awry in disorders such as addiction.

讓大腦會竭盡所能去得到獎勵。

So if we could figure out what cells they are,

正因為這些信號出差錯,才導致如癮癖性疾病，。

we could maybe find new targets

因此,如果我們能弄清楚這是哪些細胞,

for which drugs could be designed or screened against,

我們也許能找到新的標靶細胞，

or maybe places where electrodes could be put in

以設計出或篩選出適合的藥物,去對抗這類疾病，

for people who have very severe disability.

或者也可以為有非常嚴重殘疾的病患

So to do that, we came up with a very simple paradigm

在標靶細胞植入電極。

in collaboration with the Fiorella group,

要做到這一點,我們設計出一個非常簡單的模型，

where one side of this little box,

並得到菲兒瑞拉(Fiorella)公司的贊助.

if the animal goes there, the animal gets a pulse of light

在這個小盒子的一邊,

in order to make different cells in the brain sensitive to light.

如果動物跑到那兒,會被一道光照到,

So if these cells can mediate reward,

用來刺激各種不同對光敏感的腦部細胞.

the animal should go there more and more.

所以如果這些細胞可以產生被獎勵的感覺,

And so that's what happens.